Chlorine contribution to quantitative structure and activity relationship models of disinfection by -products' quantum chemical descriptors and toxicities

Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: (1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (E LUMO) via QSAR modelling and analysis; (2) to validate the models by using internal and external cross-validation techniques; (3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl ) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: (1) Linear or Multi-linear Regression (MLR); (2) Partial Least Squares (PLS); and (3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: (1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; (2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; (3) E LUMO are shown to correlate highly with the NCl for several classes of DBPs; and (4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.

A study of methods used to analyze total oil and polycyclic aromatic hydrocarbons in produced water: steps towards the validation of molecularly imprinted polymers for use in marine environmetns

Produced water is a by-product of offshore oil and gas production, and is released in large volumes when platforms are actively processing crude oil. Some pollutants are not typically removed by conventional oil/water separation methods and are discharged with produced water. Oil and grease can be found dispersed in produced water in the form of tiny droplets, and polycyclic aromatic hydrocarbons (PAHs) are commonly found dissolved in produced water. Both can have acute and chronic toxic effects in marine environments even at low exposure levels. The analysis of the dissolved and dispersed phases are a priority, but effort is required to meet the necessary detection limits. There are several methods for the analysis of produced water for dispersed oil and dissolved PAHs, all of which have advantages and disadvantages. In this work, EPA Method 1664 and APHA Method 5520 C for the determination of oil and grease will be examined and compared. For the detection of PAHs, EPA Method 525 and PAH MIPs will be compared, and results evaluated. APHA Method 5520 C Partition-Infrared Method is a liquid-liquid extraction procedure with IR determination of oil and grease. For analysis on spiked samples of artificial seawater, extraction efficiency ranged from 85 – 97%. Linearity was achieved in the range of 5 – 500 mg/L. This is a single-wavelength method and is unsuitable for quantification of aromatics and other compounds that lack sp³-hybridized carbon atoms. EPA Method 1664 is the liquid-liquid extraction of oil and grease from water samples followed by gravimetric determination. When distilled water spiked with reference oil was extracted by this procedure, extraction efficiency ranged from 28.4 – 86.2%, and %RSD ranged from 7.68 – 38.0%. EPA Method 525 uses solid phase extraction with analysis by GC-MS, and was performed on distilled water and water from St. John’s Harbour, all spiked with naphthalene, fluorene, phenanthrene, and pyrene. The limits of detection in harbour water were 0.144, 3.82, 0.119, and 0.153 g/L respectively. Linearity was obtained in the range of 0.5-10 g/L, and %RSD ranged from 0.36% (fluorene) to 46% (pyrene). Molecularly imprinted polymers (MIPs) are sorbent materials made selective by polymerizing functional monomers and crosslinkers in the presence of a template molecule, usually the analytes of interest or related compounds. They can adsorb and concentrate PAHs from aqueous environments and are combined with methods of analysis including GC-MS, LC-UV-Vis, and desorption electrospray ionization (DESI)- MS. This work examines MIP-based methods as well as those methods previously mentioned which are currently used by the oil and gas industry and government environmental agencies. MIPs are shown to give results consistent with other methods, and are a low-cost alternative improving ease, throughput, and sensitivity. PAH MIPs were used to determine naphthalene spiked into ASTM artificial seawater, as well as produced water from an offshore oil and gas operation. Linearity was achieved in the range studied (0.5 – 5 mg/L) for both matrices, with R² = 0.936 for seawater and R² = 0.819 for produced water. The %RSD for seawater ranged from 6.58 – 50.5% and for produced water, from 8.19 – 79.6%.

Sea organisms as a source of collagen-derived polymers for skin tissue engineering applications

Advanced therapies combating acute and chronic skin wounds are likely to be brought about using our knowledge of regenerative medicine coupled with appropriately tissue engineered skin substitutes. At the present time, there are no models of an artificial skin that completely replicate normal uninjured skin and they are usually accompanied by fibrotic reactions that result in the production of a scar. Natural biopolymers such as collagen have been a lot investigated as potential source of biomaterial for skin replacement in Tissue Engineering. Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role in connective tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches, as skin tissue engineering. In addition, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are skin and bone from bovine and porcine origin. However, these last carry high risk of bovine spongiform encephalopathy or transmissible spongiform encephalopathy and immunogenic responses. On the other hand, the increase of jellyfish has led us to consider this marine organism as potential collagen source for tissue engineering applications. In the present study, novel form of acid and pepsin soluble collagen were extracted from dried Rhopilema hispidum jellyfish species in an effort to obtain an alternative and safer collagen. We studied different methods of collagen purification (tissues and experimental procedures). The best collagen yield was obtained using pepsin extraction method (34.16 mg collagen/g of tissue). The isolated collagen was characterized by SDS-polyacrylamide gel electrophoresis and circular dichroism spectroscopy.

Efeito do exercício físico na estabilidade de membrana de eritrócitos

CHAPTER II - This study evaluated the effects of two different types of acute aerobic exercise on the osmotic stability of human erythrocyte membrane and on different hematological and biochemical variables that are associated with this membrane property. The study population consisted of 20 healthy and active men. Participants performed single sessions of two types of exercise. The first session consisted of 60 min of moderate-intensity continuous exercise (MICE). The second session, executed a week later, consisted of high-intensity interval exercise (HIIE) until exhaustion. The osmotic stability of the erythrocyte membrane was represented by the inverse of the salt concentration (1/H50) at the midpoint of the sigmoidal curve of dependence between the absorbance of hemoglobin and the NaCl concentration. The values of 1/H50 changed from 2.29 ± 0.1 to 2.33 ± 0.09 after MICE and from 2.30 ± 0.08 to 2.23 ± 0.12 after HIIE. In MICE has occurred an increase in the mean corpuscular volume, probably due to in vivo lysis of older erythrocytes, with preservation of cells that were larger and more resistant to in vitro lysis. The study showed that a single bout of acute exercise affected the erythrocyte osmotic stability, which increased after MICE and decreased after HIIE.

Medication review of children on long term medications:a review of the literature

INTRODUCTION: Children on long term medication may be under the care of more than one medical team including the patients GP. Children on chronic medication should be supported and their medications reviewed, especially in cases of polypharmacy. Medicines Use Reviews (MURs) were introduced into the pharmacy contract in 2005. The service was designed for community pharmacists to review patients on long term medication. The service specified that MURs were done on patients who can give consent and cannot be conducted with a parent or carer. Hence the service may be inaccessible to paediatric patients. This review aims to find studies that identify medication review services in primary care that cater for children on long term medication. METHODS: A literature search was conducted on 6th June 2015 using the keywords, ("Medication" or "review" or "Medication Review" or "Medicines use review" or "Medication use review" or "New Medicine Service") AND ("community pharmacy" OR "community pharmacist" OR "primary care" OR "General practice" OR "GP" OR "community paediatrician" OR "community pediatrician" OR "community nurse"). Bibliographic databases used were AMED, British Nursing Index, CINAHL, EMBASE, HMIC, MEDLINE, PsycINFO and Health Business Elite. Inclusion criteria were: paediatric specific medication review in primary care, for example by either a GP, community paediatrician, community nurse or community pharmacist. Exclusion criteria were studies of medication review in adults/unclear patient age and secondary care medication reviews. RESULTS: From the 417 articles, 6 relevant articles were found after abstract and full text review. 235 articles were excluded after title and abstract review (11 did not have full text in English); 96 were adult or non-age specified medication review/MUR/New Medicine Service studies; 63 referred to observational, evaluative studies of interventions in adults; 6 were non-paediatric specific systematic reviews and 17 were protocols, commentaries, news, and letters.The 6 relevant articles consisted of 1 literature review (published 2004), 3 research articles and 1 published protocol. The literature review[1] recommended that children's long term medication should be reviewed. The published protocol stated that the NMS minimum age for inclusion in the trial was for children aged over 13 years of age. The four studies were related to psychiatrists reviewing paediatric mental health patients in the USA, a pharmacist using Drug Related Problem to review patients in GP practices in Australia, a UK study based on an information prescription concept by providing children dispensed medications in community pharmacy with signposting them to health information and one GP practice based study observing pharmaceutical care issues in children and adults. CONCLUSION: The results show that there are currently no known studies on medication use reviews specific to children, whereas in adults, published evaluations are available. The terms of the MUR policy restrict children's access to the service and so more studies are necessary to determine whether children could benefit from such access.

Guideline-based decision support has a small, non-sustained effect on transthoracic echocardiography ordering frequency.

BACKGROUND: Guidance for appropriate utilisation of transthoracic echocardiograms (TTEs) can be incorporated into ordering prompts, potentially affecting the number of requests. METHODS: We incorporated data from the 2011 Appropriate Use Criteria for Echocardiography, the 2010 National Institute for Clinical Excellence Guideline on Chronic Heart Failure, and American College of Cardiology Choosing Wisely list on TTE use for dyspnoea, oedema and valvular disease into electronic ordering systems at Durham Veterans Affairs Medical Center. Our primary outcome was TTE orders per month. Secondary outcomes included rates of outpatient TTE ordering per 100 visits and frequency of brain natriuretic peptide (BNP) ordering prior to TTE. Outcomes were measured for 20 months before and 12 months after the intervention. RESULTS: The number of TTEs ordered did not decrease (338±32 TTEs/month prior vs 320±33 afterwards, p=0.12). Rates of outpatient TTE ordering decreased minimally post intervention (2.28 per 100 primary care/cardiology visits prior vs 1.99 afterwards, p<0.01). Effects on TTE ordering and ordering rate significantly interacted with time from intervention (p<0.02 for both), as the small initial effects waned after 6 months. The percentage of TTE orders with preceding BNP increased (36.5% prior vs 42.2% after for inpatients, p=0.01; 10.8% prior vs 14.5% after for outpatients, p<0.01). CONCLUSIONS: Ordering prompts for TTEs initially minimally reduced the number of TTEs ordered and increased BNP measurement at a single institution, but the effect on TTEs ordered was likely insignificant from a utilisation standpoint and decayed over time.

Development and Characterization of Monovalent and Bivalent RNA Aptamers Targeting the Common Pathway of Coagulation

Anticoagulant agents are commonly used drugs to reduce blood coagulation in acute and chronic clinical settings. Many of these drugs target the common pathway of coagulation because it is critical for thrombin generation and disruption of this portion of the pathway has profound effects on the hemostatic process. Currently available drugs for these indications struggle with balancing desired activity with immunogenicity and poor reversibility or irreversibility in the event of hemorrhage. While improvements are being made with the current drugs, new drugs with better therapeutic indices are needed for surgical intervention and chronic indications to prevent thrombosis from occurring.

A class of therapeutics known as aptamers may be able to meet the need for safer anticoagulant agents. Aptamer are short single-stranded RNA oligonucleotides that adopt specific secondary and tertiary structures based upon their sequence. They can be generated to both enzymes and cofactors because they derive their inhibitory activity by blocking protein-protein interactions, rather than active site inhibition. They inhibit their target proteins with a high level of specificity and bind with high affinity to their target. Additionally, they can be reversed using two different antidote approaches, specific oligonucleotide antidotes, or with cationic, “universal” antidotes. The reversal of their activity is both rapid and durable.

The ability of aptamers to be generated to cofactors has been conclusively proven by generating an aptamer targeting the common pathway coagulation cofactor, Factor V (FV). We developed two aptamers with anticoagulant ability that bind to both FV and FVa, the active cofactor. Both aptamers were truncated to smaller functional sizes and had specific point mutant aptamers developed for use as controls. The anticoagulant activity of both aptamer-mutant pairs was characterized using plasma-based clotting assays and whole blood assays. The mechanism of action resulting in anticoagulant activity was assessed for one aptamer. The aptamer was found to block FVa docking to membrane surfaces, a mechanism not previously observed in any of our other anticoagulant aptamers.

To explore development of aptamers as anticoagulant agents targeting the common pathway for surgical interventions, we fused two anticoagulant aptamers targeting Factor X and prothrombin into a single molecule. The bivalent aptamer was truncated to a minimal size while maintaining robust anticoagulant activity. Characterization of the bivalent aptamer in plasma-based clotting assays indicated we had generated a very robust anticoagulant therapeutic. Furthermore, we were able to simultaneously reverse the activity of both aptamers with a single oligonucleotide antidote. This rapid and complete reversal of anticoagulant activity is not available in the antithrombotic agents currently used in surgery.

Chlorine Contribution to Quantitative Structure and Activity Relationship Models of Disinfection By-Products' Quantum Chemical Descriptors and Toxicities

Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: 1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (ELUMO) via QSAR modelling and analysis; 2) to validate the models by using internal and external cross-validation techniques; 3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: 1) Linear or Multi-linear Regression (MLR); 2) Partial Least Squares (PLS); and 3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: 1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; 2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; 3) ELUMO are shown to correlate highly with the NCl for several classes of DBPs; and 4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.

Evaluation of an alternative spectroscopic approach for aflatoxin analysis: Comparative analysis of food and feed samples with UPLC-MS/MS

Increasing research has highlighted the effects of changing climates on the occurrence and prevalence of toxigenic Aspergillus species producing aflatoxins. There is concern of the toxicological effects to human health and animal productivity following acute and chronic exposure that may affect the future ability to provide safe and sufficient food globally. Considerable research has focused on the detection of these toxins, based on the physicochemical and biochemical properties of the aflatoxin compounds, in agricultural products for human and animal consumption. As improvements in food security continue more regulations for acceptable levels of aflatoxins have arisen globally; the most stringent in Europe. These regulations are important for developing countries as aflatoxin occurrence is high significantly effecting international trade and the economy. In developed countries analytical approaches have become highly sophisticated, capable of attaining results with high precision and accuracy, suitable for regulatory laboratories. Regrettably, many countries that are affected by aflatoxin contamination do not have resources for high tech HPLC and MS instrumentation and require more affordable, yet robust equally accurate alternatives that may be used by producers, processors and traders in emerging economies. It is especially important that those companies wishing to exploit the opportunities offered by lucrative but highly regulated markets in the developed world, have access to analytical methods that will ensure that their exports meet their customers quality and safety requirements.

This work evaluates the ToxiMet system as an alternative approach to UPLC–MS/MS for the detection and determination of aflatoxins relative to current European regulatory standards. Four commodities: rice grain, maize cracked and flour, peanut paste and dried distillers grains were analysed for natural aflatoxin contamination. For B1 and total aflatoxins determination the qualitative correlation, above or below the regulatory limit, was good for all commodities with the exception of the dried distillers grain samples for B1 for which no calibration existed. For B1 the quantitative R² correlations were 0.92, 0.92, 0.88 (<250 μg/kg) and 0.7 for rice, maize, peanuts and dried distillers grain samples respectively whereas for total aflatoxins the quantitative correlation was 0.92, 0.94, 0.88 and 0.91. The ToxiMet system could be used as an alternative for aflatoxin analysis for current legislation but some consideration should be given to aflatoxin M1 regulatory levels for these commodities considering the high levels detected in this study especially for maize and peanuts

Fast and sensitive aflatoxin B1 and total aflatoxins ELISAs for analysis of peanuts, maize and feed ingredients

Aflatoxins are a group of carcinogenic compounds produced by Aspergillus fungi that can grow on different agricultural crops. Both acute and chronic exposure to these mycotoxins can cause serious illness. Due to the high occurrence of aflatoxins in crops worldwide fast and cost-effective analytical methods are required for the identification of contaminated agricultural commodities before they are processed into final products and placed on the market. In order to provide new tools for aflatoxin screening two prototype fast ELISA methods: one for the detection of aflatoxin B₁ and the other for total aflatoxins were developed. Seven monoclonal antibodies with unique high sensitivity and at the same time good cross-reactivity profiles were produced. The monoclonal antibodies were characterized and two antibodies showing IC₅₀ of 0.037 ng/mL and 0.031 ng/mL for aflatoxin B₁ were applied in simple and fast direct competitive ELISA tests. The methods were validated for peanut matrix as this crop is one of the most affected by aflatoxin contamination. The detection capabilities of aflatoxin B₁ and total aflatoxins ELISAs were 0.4 μg/kg and 0.3 μg/kg for aflatoxin B₁, respectively, which are one of the lowest reported values. Total aflatoxins ELISA was also validated for the detection of aflatoxins B₂, G₁ and G₂. The application of the developed tests was demonstrated by screening 32 peanut samples collected from the UK retailers. Total aflatoxins ELISA was further applied to analyse naturally contaminated maize porridge and distiller's dried grain with solubles samples and the results were correlated with these obtained by UHPLC-MS/MS method.

Modifications neurométaboliques et microstructurales à la suite d'une commotion cérébrale chez les athlètes féminines.

L’utilisation de méthodes d’investigation cérébrale avancées a permis de mettre en évidence la présence d’altérations à court et à long terme à la suite d’une commotion cérébrale. Plus spécifiquement, des altérations affectant l’intégrité de la matière blanche et le métabolisme cellulaire ont récemment été révélées par l’utilisation de l’imagerie du tenseur de diffusion (DTI) et la spectroscopie par résonance magnétique (SRM), respectivement. Ces atteintes cérébrales ont été observées chez des athlètes masculins quelques jours après la blessure à la tête et demeuraient détectables lorsque les athlètes étaient à nouveau évalués six mois post-commotion. En revanche, aucune étude n’a évalué les effets neurométaboliques et microstructuraux dans la phase aigüe et chronique d’une commotion cérébrale chez les athlètes féminines, malgré le fait qu’elles présentent une susceptibilité accrue de subir ce type de blessure, ainsi qu’un nombre plus élevé de symptômes post-commotionnels et un temps de réhabilitation plus long. Ainsi, les études composant le présent ouvrage visent globalement à établir le profil d’atteintes microstructurales et neurométaboliques chez des athlètes féminines par l’utilisation du DTI et de la SRM. La première étude visait à évaluer les changements neurométaboliques au sein du corps calleux chez des joueurs et joueuses de hockey au cours d’une saison universitaire. Les athlètes ayant subi une commotion cérébrale pendant la saison ont été évalués 72 heures, 2 semaines et 2 mois après la blessure à la tête en plus des évaluations pré et post-saison. Les résultats démontrent une absence de différences entre les athlètes ayant subi une commotion cérébrale et les athlètes qui n’en ont pas subie. De plus, aucune différence entre les données pré et post-saison a été observée chez les athlètes masculins alors qu’une diminution du taux de N-acetyl aspartate (NAA) n’a été mise en évidence chez les athlètes féminines, suggérant ainsi un impact des coups d’intensité sous-clinique à la tête. La deuxième étude, qui utilisait le DTI et la SRM, a révélé des atteintes chez des athlètes féminines commotionnées asymptomatiques en moyenne 18 mois post-commotion. Plus spécifiquement, la SRM a révélé une diminution du taux de myo-inositol (mI) au sein de l’hippocampe et du cortex moteur primaire (M1) alors que le DTI a mis en évidence une augmentation de la diffusivité moyenne (DM) dans plusieurs faisceaux de matière blanche. De iii plus, une approche par région d’intérêt a mis en évidence une diminution de la fraction d’anisotropie (FA) dans la partie du corps calleux projetant vers l’aire motrice primaire. Le troisième article évaluait des athlètes ayant subi une commotion cérébrale dans les jours suivant la blessure à la tête (7-10 jours) ainsi que six mois post-commotion avec la SRM. Dans la phase aigüe, des altérations neuropsychologiques combinées à un nombre significativement plus élevé de symptômes post-commotionnels et dépressifs ont été trouvés chez les athlètes féminines commotionnées, qui se résorbaient en phase chronique. En revanche, aucune différence sur le plan neurométabolique n’a été mise en évidence entre les deux groupes dans la phase aigüe. Dans la phase chronique, les athlètes commotionnées démontraient des altérations neurométaboliques au sein du cortex préfrontal dorsolatéral (CPDL) et M1, marquées par une augmentation du taux de glutamate/glutamine (Glx). De plus, une diminution du taux de NAA entre les deux temps de mesure était présente chez les athlètes contrôles. Finalement, le quatrième article documentait les atteintes microstructurales au sein de la voie corticospinale et du corps calleux six mois suivant une commotion cérébrale. Les analyses n’ont démontré aucune différence au sein de la voie corticospinale alors que des différences ont été relevées par segmentation du corps calleux selon les projections des fibres calleuses. En effet, les athlètes commotionnées présentaient une diminution de la DM et de la diffusivité radiale (DR) au sein de la région projetant vers le cortex préfrontal, un volume moindre des fibres de matière blanche dans la région projetant vers l’aire prémotrice et l’aire motrice supplémentaire, ainsi qu’une diminution de la diffusivité axiale (DA) dans la région projetant vers l’aire pariétale et temporale. En somme, les études incluses dans le présent ouvrage ont permis d’approfondir les connaissances sur les effets métaboliques et microstructuraux des commotions cérébrales et démontrent des effets délétères persistants chez des athlètes féminines. Ces données vont de pair avec la littérature scientifique qui suggère que les commotions cérébrales n’entraînent pas seulement des symptômes temporaires.

The Cardiovascular Pathology of Stimulant Overdose Decedents in King County, Washington

Thesis (Master's)--University of Washington, 2016-09

Should I stay or should I go – Factors associated with hospitalization risk among older persons in Sweden

An increasingly older population will most likely lead to greater demands on the health care system, as older age is associated with an increased risk of having acute and chronic conditions. The number of diseases or disabilities is not the only marker of the amount of health care utilized, as persons may seek hospitalization without a disease and/or illness that requires hospital healthcare. Hospitalization may pose a severe risk to older persons, as exposure to the hospital environment may lead to increased risks of iatrogenic disorders, confusion, falls and nosocomial infections, i.e., disorders that may involve unnecessary suffering and lead to serious consequences. Aims: The overall aim of this thesis was to describe and explore individual trajectories of cognitive development in relation to hospitalization and risk factors for hospitalization among older persons living in different accommodations in Sweden and to explore older persons' reasons for being transferred to a hospital. Methods: The study designs were longitudinal, prospective and descriptive, and both quantitative and qualitative methods were used. Specifically, latent growth curve modelling was used to assess the association of cognitive development with hospitalization. The Cox proportional hazards regression model was used to analyse factors associated with hospitalization risk overtime. In addition, an explorative descriptive design was used to explore how home health care patients experienced and perceived their decision to seek hospital care. Results: The most common reasons for hospitalization were cardiovascular diseases, which caused more than one-quarter of first hospitalizations among the persons living in ordinary housing and nursing home residents (NHRs). The persons who had been hospitalized had a lower mean level of cognitive performance in general cognition, verbal, spatial/fluid, memory and processing speed abilities compared to those who had not been hospitalized. Significantly steeper declines in general cognition, spatial/fluid and processing speed abilities were observed among the persons who had been hospitalized. Cox proportional hazards regression analysis showed that the number of diseases, number of drugs used, having experienced a fall and being assessed as malnourished according to the Mini Nutritional Assessment scale were related to an increased hospitalization risk among the NHRs. Among the older persons living in ordinary housing, the risk factors for hospitalization were related to marital status, i.e., unmarried persons and widows/widowers had a decreased hospitalization risk. In addition, among social factors, receipt of support from relatives was related to an increased hospitalization risk, while receipt of support from friends was related to a decreased risk. The number of illnesses was not associated with the hospitalization risk for older persons in any age group or for those of either sex, when controlling for other variables. The older persons who received home health care described different reasons for their decisions to seek hospital care. The underlying theme of the home health care patients’ perceptions of their transfer to a hospital involved trust in hospitals. This trust was shared by the home health care patients, their relatives and the home health care staff, according to the patients. Conclusions: This thesis revealed that middle-aged and older persons who had been hospitalized exhibited a steeper decline in cognition. Specifically, spatial/fluid, processing speed, and general cognitive abilities were affected. The steeper decline in cognition among those who had been hospitalized remained even after controlling for comorbidities. The most common causes of hospitalization among the older persons living in ordinary housing and in nursing homes were cardiovascular diseases, tumours and falls. Not only health-related factors, such as the number of diseases, number of drugs used, and being assessed as malnourished, but also social factors and marital status were related to the hospitalization risk among the older persons living in ordinary housing and in nursing homes. Some risk factors associated with hospitalization differed not only between the men and women but also among the different age groups. The information provided in this thesis could be applied in care settings by professionals who interact with older persons before they decide to seek hospital care. To meet the needs of an older population, health care systems need to offer the proper health care at the most appropriate level, and they need to increase integration and coordination among health care delivered by different care services.

Sinusite maxilar odontogénica

O seio maxilar é o seio paranasal mais susceptível a invasões bacterianas, tanto pelo óstio nasal, como pela cavidade oral. As sinusites maxilares têm como causas mais frequentes, as infecções víricas, rinites alérgicas ou não alérgicas, variações anatómicas, diabetes mellitus, fumar, nadar, mergulhar, escalar a altas atitudes, e as infecções e tratamentos dentários. A pesquisa bibliográfica, foi realizada sem quaisquer limitações temporais, com restrição linguística a Português, Espanhol e Inglês, sendo excluídos os artigos de outros idiomas; em vários livros e revistas, assim como artigos científicos obtidos, entre Maio e Julho de 2015, nos motores de busca Pubmed, ScienceDirect, Scielo, Elsevier e B-on. A sinusite maxilar odontogénica é uma doença infecto-inflamatória, habitualmente associada à ruptura da membrana de Schneider e a processos infecciosos dentários crónicos. Causa hiperplasia e hipertrofia da mucosa, o que origina sinais e sintomas próprios, assim como mudanças radiográficas perceptíveis. Existem diferentes etiologias de causa odontogénica: cárie, doença periodontal, quistos odontogénicos e iatrogenia – tratamento endodôntico não cirúrgico, cirurgia endodôntica, comunicações oro-antrais, implantes dentários, elevação do seio maxilar, cirurgia pré-protética e cirurgia ortognática – sendo que a iatrogenia é a mais comum (cerca de 56%). Esta patologia afecta com mais frequência indivíduos dos 42,7 aos 51, 7 anos, e preferencialmente a região molar, seguida dos pré-molares e em alguns casos, caninos. Os organismos que dominam na fase aguda e crónica, são sensivelmente os mesmos, mas em número diferente, e existe uma conexão entre a flora comensal periapical e a flora patogénica em caso de sinusite maxilar odontogénica. O diagnóstico é essencialmente clínico, no entanto existem diferentes exames complementares para confirmarem ou formarem o diagnóstico. Pela grande acessibilidade ao método radiográfico, torna-se fundamental que o médico dentista saiba diferencial as diversas patologias que afectam o seio maxilar. O tratamento abrange a eliminação da causa dentária e o tratamento farmacológico, da infecção, essencialmente à base de antibióticos, e da dor se esta existir. E o tratamento cirúrgico, que contempla a punção-lavagem sinusal, antrostomia intranasal, técnica de Caldwell-Luc e cirurgia sinusal endoscópica. Concluindo, o médico dentista deve ter um amplo conhecimento sobre esta patologia para que a possa reconhecer, tratar ou preveni-la.

Avaliação do potencial cancerigénico de microcistinas (cianotoxinas)

Tese de doutoramento em Farmácia (Toxicologia), apresentada à Faculdade de Farmácia da Universidade de Lisboa, 2009.